Oral Presentation ESA-SRB-NZSE-CaSR 2026 in conjunction with ENSA

Elevated ambient temperature modifies seminal plasma composition and endometrial transcriptional responses after mating (144058)

Hon (Dexter) Y Chan 1 , Shanu Parameswaran 2 3 , Ha M Tran 1 , Elizabeth Torres-Arce 2 3 , Shannon P Smyth 4 , David A Skerrett-Byrne 2 5 6 7 8 , Cottrell T Tamessar 2 3 9 , Jacinta H Martin 2 3 , Lily A Macdougall 2 3 , Natalie A Trigg 2 3 , Jessica E Mulhall 2 3 , Amanda A Anderson 2 3 , Brett Nixon 2 3 , David J Sharkey 1 , Sarah A Robertson 1 , John E Schjenken 2 3
  1. Robinson Research Institute and School of Pharmacy and Biomedical Sciences, College of Health, Adelaide University, Adelaide, South Australia, Australia
  2. Hunter Medical Research Institute, Reproductive and Family Health Research Program, New Lambton Heights, New South Wales, Australia
  3. Centre for Reproductive Science, School of Science, College of Engineering, Science and Environment, University of Newcastle, Callaghan, NSW, Australia
  4. School of Biosciences, Faculty of Science, Bio21 Institute, The University of Melbourne, Parkville, Victoria, Australia
  5. Institute of Experimental Genetics, German Research Centre for Environmental Health, Helmholtz Zentrum Munchen, Neuherberg, Germany
  6. Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC, Australia
  7. Therapeutics Discovery and Vascular Function in Pregnancy Group, Department of Obstetrics, Gynaecology and Newborn Health, Melbourne Medical School, The University of Melbourne, Heidelberg, VIC, Australia
  8. German Centre for Diabetes Research (DZD), Neuherberg, Germany
  9. Systems Biology Research Center, School of Bioscience, University of Skovde, Skovde, Sweden

Background: Extreme weather events, including heatwaves, are expected to increase in frequency and intensity over coming decades, posing a risk to reproductive health. We have shown that modest increases in ambient temperature affect male reproductive function through alterations to the sperm genome/epigenome. However, male reproductive capacity also depends on the ability of seminal plasma to induce a permissive female reproductive environment. Here, we investigated whether elevated ambient temperature influences how males induce a female response to seminal fluid.

Methods: Adult male Swiss mice were exposed to either control (21°C) or ‘heatwave’ conditions (8h at 35°C, 16h at 25°C) for 7-days. Following treatment, males were mated with receptive female Swiss mice, and endometrial tissue was collected 8h after mating. Virgin estrus females served as unmated controls. Endometrial gene expression was assessed by RNA-sequencing with differentially expressed genes defined as -1.5≤FC≥1.5, p.adj≤0.05. Candidate seminal plasma signalling mediators Ingenuity Pathway Analysis Upstream Regulator analysis and quantified in seminal vesicle fluid by Luminex assay.

Results: Endometrial tissue was more responsive to seminal fluid from heat-treated males (362 up-, 691 down-regulated) compared to control males (169 up-regulated, 401 down-regulated).  Direct comparison of heat- compared to control-mated groups identified 180 up- and 30 down-regulated genes, with differentially regulated genes associated with the activation of immune- and receptivity-associated signalling pathways (p≤0.05). Predicted upstream regulators included interferon (IFN)G, interleukin (IL)6, IL17 and transforming growth factor (TGF)B (all p≤0.05). Consistent with these predictions, Luminex analysis of seminal vesicle fluid revealed increased concentrations of IFNG, IL17, IL6 and TGFB1 in seminal plasma of heat-treated compared to control males.

Conclusions: These findings demonstrate that seminal plasma composition is altered by elevated ambient temperature, and that heat-induced changes in seminal plasma influence the female reproductive tract immune response after mating, with potential consequences for fetal development and offspring health.